Lactoferrin in the treatment of malignant neoplasms and other hyperproliferative diseases

Abstract

The present invention relates to methods of treating a hyperproliferative disease by administering a composition of lactoferrin alone or in combination with standard anti-cancer therapies.

1 . A method of treating a hyperproliferative disease comprising the step of administering orally to a subject a human lactoferrin composition in an amount sufficient to provide an improvement in the hyperproliferative disease in said subject. 
     
     
         2 . The method of  claim 1 , wherein said human lactoferrin composition is dispersed in a pharmaceutically acceptable carrier. 
     
     
         3 . The method of  claim 1 , wherein said human lactoferrin is recombinant human lactoferrin. 
     
     
         4 . The method of  claim 1  further comprising administering an antacid in conjunction with said human lactoferrin composition. 
     
     
         5 . The method of  claim 1 , wherein the amount of the composition that is administered is about 1 mg to about 100 g per day. 
     
     
         6 . The method of  claim 1 , wherein the amount of the composition that is administered is about 20 mg to about 10 g per day. 
     
     
         7 . The method of  claim 1 , wherein the hyperproliferative disease is further defined as cancer. 
     
     
         8 . The method of  claim 7 , wherein the cancer comprises a neoplasm. 
     
     
         9 . The method of  claim 8 , wherein the neoplasm is selected from the group consisting of melanoma, non-small cell lung, small-cell lung, lung hepatocarcinoma, retinoblastoma, astrocytoma, gliobastoma, leukemia, neuroblastoma, squamous cell, head, neck, gum, tongue, breast, pancreatic, prostate, renal, bone, testicular, ovarian, mesothelioma, sarcoma, cervical, gastrointestinal, lymphoma, brain, colon, and bladder. 
     
     
         10 . The method of  claim 7 , wherein the neoplasm is a hematopoietic neoplasm. 
     
     
         11 . The method of  claim 10 , wherein the hematopoietic neoplasm is selected from the group consisting of acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, juvenile myelomonocyte leukemia, multiple myeloma, and chronic lymphocytic leukemia. 
     
     
         12 . The method of  claim 1 , wherein the hyperproliferative disease is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, osteoarthritis, leiomyomas, adenomas, lipomas, hemangiomas, fibromas, vascular occlusion, restenosis, atherosclerosis, pre-neoplastic lesions, carcinoma in situ, oral hairy leukoplakia, and psoriasis. 
     
     
         13 . A method of treating a hyperproliferative disease comprising the step of supplementing the mucosal immune system in a subject by increasing the amount of human lactoferrin in the gastrointestinal tract. 
     
     
         14 . The method of  claim 13 , wherein said human lactoferrin is recombinant human lactoferrin. 
     
     
         15 . The method of  claim 13 , wherein human lactoferrin is administered orally. 
     
     
         16 . The method of  claim 13 , wherein human lactoferrin stimulates the production of interleukin-18. 
     
     
         17 . The method of  claim 13 , wherein human lactoferrin stimulates the production of GM-CSF. 
     
     
         18 . A method of enhancing a mucosal immune response in the gastrointestinal tract in a subject comprising the step of administering orally to said subject a human lactoferrin. 
     
     
         19 . The method of  claim 18 , wherein said human lactoferrin is recombinant human lactoferrin. 
     
     
         20 . The method of  claim 18 , wherein the human lactoferrin stimulates interleukin-18 in the gastrointestinal tract. 
     
     
         21 . The method of  claim 20 , wherein interleukin-18 stimulates the production, maturation or activity of immune cells. 
     
     
         22 . The method of  claim 21 , wherein the immune cells are T lymphocytes or natural killer cells. 
     
     
         23 . The method of  claim 22 , wherein the T lymphocytes are selected from the group consisting of CD4+, CD8+ and CD3+ cells. 
     
     
         24 . The method of  claim 17 , wherein the human lactoferrin stimulates GM-CSF in the gastrointestinal tract. 
     
     
         25 . The method of  claim 20 , wherein GM-CSF stimulates the production, maturation or activity of immune cells. 
     
     
         26 . The method of  claim 25 , wherein the immune cells are dendritic or other antigen presenting cells. 
     
     
         27 . The method of  claim 18 , wherein said subject suffers from a hyperproliferative disease. 
     
     
         28 . The method of  claim 1  further comprising additionally administering chemotherapy, immunotherapy, surgery, biotherapy, radiotherapy or a combination thereof. 
     
     
         29 . The method of  claim 28 , wherein the chemotherapy is a platinum based agent. 
     
     
         30 . The method of  claim 29  where the platinum based agent in cisplatin. 
     
     
         31 . The method of  claim 28 , wherein the chemotherapy is a taxane based agent. 
     
     
         32 . The method of  claim 31 , wherein the chemotherapy is docetaxel. 
     
     
         33 . The method of  claim 1  further comprising additionally administering radiotherapy. 
     
     
         34 . A method of reducing growth of a neoplasm in a subject comprising the step of administering orally to the subject a human lactoferrin composition in an amount sufficient to reduce the growth of the neoplasm in said subject. 
     
     
         35 . The method of  claim 34  further comprising additionally administering chemotherapy, immunotherapy, surgery, biotherapy, radiotherapy or a combination thereof. 
     
     
         36 . The method of  claim 35 , wherein the chemotherapy is a platinum based chemotherapy. 
     
     
         37 . The method of  claim 36 , wherein the platinum based chemotherapy is cisplatin. 
     
     
         38 . The method of  claim 35 , wherein the chemotherapy is a taxane based chemotherapy. 
     
     
         39 . The method of  claim 37  wherein the chemotherapy is a docetaxel. 
     
     
         40 . The method of  claim 34  further comprising additionally administering radiotherapy. 
     
     
         41 . A method of treating a hyperproliferative disease comprising administering orally to a subject a human lactoferrin composition in combination with chemotherapy, biotherapy, immunotherapy, surgery or radiotherapy. 
     
     
         42 . A method of treating a hyperproliferative disease comprising the step of administering intravenously to a subject a lactoferrin composition in an amount sufficient to provide an improvement in the hyperproliferative disease in said subject. 
     
     
         43 . The method of  claim 42 , wherein said lactoferrin composition is dispersed in a pharmaceutically acceptable carrier. 
     
     
         44 . The method of  claim 42 , wherein said lactoferrin is mammalian lactoferrin. 
     
     
         45 . The method of  claim 44 , wherein said lactoferrin is human. 
     
     
         46 . The method of  claim 44 , wherein said lactoferrin is bovine. 
     
     
         47 . The method of  claim 44 , wherein said lactoferrin is recombinant lactoferrin. 
     
     
         48 . The method of  claim 42 , wherein the amount of the composition that is administered is about 0.1 μg to about 10 g per day. 
     
     
         49 . The method of  claim 42 , wherein the amount of the composition that is administered is about 1 μg to about 1 g per day. 
     
     
         50 . The method of  claim 42 , wherein the hyperproliferative disease is further defined as cancer. 
     
     
         51 . The method of  claim 50 , wherein the cancer comprises a neoplasm. 
     
     
         52 . The method of  claim 51 , wherein the neoplasm is selected from the group consisting of melanoma, non-small cell lung, small-cell lung, lung hepatocarcinoma, retinoblastoma, astrocytoma, gliobastoma, leukemia, neuroblastoma, squamous cell, head, neck, gum, tongue, breast, pancreatic, prostate, renal, bone, testicular, ovarian, mesothelioma, sarcoma, cervical, gastrointestinal, lymphoma, brain, colon, and bladder. 
     
     
         53 . The method of  claim 52 , wherein the neoplasm is a hematopoietic neoplasm. 
     
     
         54 . The method of  claim 53 , wherein the hematopoietic neoplasm is selected from the group consisting of acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, juvenile myelomonocyte leukemia, multiple myeloma, and chronic lymphocytic leukemia. 
     
     
         55 . The method of  claim 42 , wherein the hyperproliferative disease is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, osteoarthritis, leiomyomas, adenomas, lipomas, hemangiomas, fibromas, vascular occlusion, restenosis, atherosclerosis, pre-neoplastic lesions, carcinoma in situ, oral hairy leukoplakia, and psoriasis. 
     
     
         56 . A method of treating a hyperproliferative disease comprising the step of supplementing a systemic immune system in a subject by increasing the amount of lactoferrin in the systemic circulation. 
     
     
         57 . The method of  claim 56 , wherein said lactoferrin is recombinant lactoferrin. 
     
     
         58 . The method of  claim 56 , wherein said lactoferrin is administered intravenously. 
     
     
         59 . The method of  claim 56 , wherein said lactoferrin stimulates the production of interleukin-18. 
     
     
         60 . The method of  claim 56 , wherein said lactoferrin stimulates the production of GM-CSF. 
     
     
         61 . A method of enhancing a systemic immune response following the step of administering intravenously to said subject a lactoferrin composition. 
     
     
         62 . The method of  claim 61 , wherein said lactoferrin is recombinant lactoferrin. 
     
     
         63 . The method of  claim 61 , wherein said lactoferrin stimulates interleukin-18. 
     
     
         64 . The method of  claim 61 , wherein said lactoferrin stimulates GM-CSF. 
     
     
         65 . The method of  claim 63 , wherein interleukin-18 stimulates the production, maturation or activity of immune cells. 
     
     
         66 . The method of  claim 65 , wherein the immune cells are T lymphocytes or natural killer cells. 
     
     
         67 . The method of  claim 66 , wherein the T lymphocytes are selected from the group consisting of CD4+, CD8+ and CD3+ cells. 
     
     
         68 . The method of  claim 63 , wherein GM-CSF stimulates the production, maturation or activity of immune cells. 
     
     
         69 . The method of  claim 65 , wherein the immune cells are dendritic or other antigen presenting cells. 
     
     
         70 . The method of  claim 61 , wherein said subject suffers from a hyperproliferative disease. 
     
     
         71 . The method of  claim 42  further comprising additionally administering chemotherapy, immunotherapy, surgery, biotherapy, radiotherapy or a combination thereof. 
     
     
         72 . A method of treating a hyperproliferative disease comprising administering intravenously to a subject a lactoferrin composition in combination with chemotherapy, biotherapy, immunotherapy, surgery or radiotherapy. 
     
     
         73 . A method of treating a hyperproliferative disease comprising the step of administering topically to a subject a lactoferrin composition in an amount sufficient to provide an improvement in the hyperproliferative disease in said subject. 
     
     
         74 . The method of  claim 73 , wherein said lactoferrin composition is dispersed in a pharmaceutically acceptable carrier. 
     
     
         75 . The method of  claim 73 , wherein the amount of the composition that is administered is about 0.1 μg to about 10 g per day. 
     
     
         76 . The method of  claim 73 , wherein the composition is a topical gel, a solution, capsule or a tablet having a lactoferrin concentration of about 0.01% to about 20%. 
     
     
         77 . The method of  claim 76 , wherein the lactoferrin concentration of about 1.0% to about 8.5%. 
     
     
         78 . The method of  claim 73 , wherein the hyperproliferative disease is further defined as cancer. 
     
     
         79 . The method of  claim 78 , wherein the cancer comprises a neoplasm. 
     
     
         80 . The method of  claim 79 , wherein the neoplasm is selected from the group consisting of melanoma, non-small cell lung, small-cell lung, lung hepatocarcinoma, retinoblastoma, astrocytoma, gliobastoma, leukemia, neuroblastoma, squamous cell, head, neck, gum, tongue, breast, pancreatic, prostate, renal, bone, testicular, ovarian, mesothelioma, sarcoma, cervical, gastrointestinal, lymphoma, brain, colon, and bladder. 
     
     
         81 . A method of enhancing a local or systemic immune response following the step of administering topically to said subject a lactoferrin composition. 
     
     
         82 . The method of  claim 81 , wherein said lactoferrin is recombinant lactoferrin. 
     
     
         83 . The method of  claim 81 , wherein said lactoferrin stimulates interleukin-18. 
     
     
         84 . The method of  claim 81 , wherein said lactoferrin stimulates GM-CSF. 
     
     
         85 . The method of  claim 83 , wherein interleukin-18 stimulates the production, maturation or activity of immune cells. 
     
     
         86 . The method of  claim 85 , wherein the immune cells are T lymphocytes or natural killer cells. 
     
     
         87 . The method of  claim 86 , wherein the T lymphocytes are selected from the group consisting of CD4+, CD8+ and CD3+ cells. 
     
     
         88 . The method of  claim 84 , wherein GM-CSF stimulates the production, maturation or activity of immune cells. 
     
     
         89 . The method of  claim 88 , wherein the immune cells are dendritic or other antigen presenting cells. 
     
     
         90 . The method of  claim 81 , wherein said subject suffers from a hyperproliferative disease. 
     
     
         91 . The method of  claim 81  further comprising additionally administering chemotherapy, immunotherapy, surgery, biotherapy, radiotherapy or a combination thereof. 
     
     
         92 . A method of treating a hyperproliferative disease comprising administering topically to a subject a lactoferrin composition in combination with chemotherapy, biotherapy, immunotherapy, surgery or radiotherapy. 
     
     
         93 . A method of treating a hyperproliferative disease comprising the step of supplementing a local or systemic immune system in a subject by increasing the amount of lactoferrin in the vicinity of a tumor. 
     
     
         94 . The method of  claim 93 , wherein said lactoferrin is recombinant lactoferrin. 
     
     
         95 . The method of  claim 93 , wherein said lactoferrin is administered topically. 
     
     
         96 . The method of  claim 95 , wherein said lactoferrin stimulates the production of interleukin-18. 
     
     
         97 . The method of  claim 95 , wherein said lactoferrin stimulates the production of GM-CSF. 
     
     
         98 . A method of stimulating interleukin-18 in a subject comprising the step of administering to said subject a lactoferrin composition. 
     
     
         99 . A method of stimulating GM-CSF in a subject comprising the step of administering to said subject a lactoferrin composition.